Hypothesis: Glatiramer acetate should have a beneficial effect in slowing progression of disability in patients with primary progressive multiple sclerosis (PPMS). Background: MS can have either a relapsing-remitting or a progressive course. Many patients start with a relapsing-remitting course and enter a progressive phase after years of disease. This is called secondary progressive MS. About 20% of MS patients have PPMS with a progressive course from onset with no relapses or remissions. The PPMS group differs from the relapsing-remitting and secondary progressive groups in certain immunologic and radiologic characteristics. There are now three drugs available in the US which have been shown to decrease the number of exacerbations and slow the accumulation of disability in relapsing-remitting MS. These include two formulations of interferon-b and glatiramer acetate. Interferon-b has also been shown to be effective in slowing accummulation of disability in secondary progressive MS. There are no drugs demonstrated to be beneficial in PPMS, and to our knowledge, no trials of interferon-b in PPMS are planned. Specific Aims: The overall objective of this study is to demonstrate the efficacy, safety, and tolerability of glatiramer acetate in PPMS. The primary efficacy endpoint is the time to confirmed disease progression as measured by the Kurtke EDSS, a standard clinical scale for rating disability in MS. Safety assessment will be based on reported adverse events, vital signs, and laboratory data. Tolerability will be assessed on the number of patients completing the study. Secondary endpoints for efficacy include the effect of glatiramer on the proportion of progression-free patients, categorical change in EDSS from baseline, change from baseline in the time taken to walk 25 feet, and changes in lesion volume on brain MRI. Methods: Nine hundred patients will be enrolled at 55 centers in the US and Canada. One-third of patients will be on placebo, and 2/3 on active drug. The drug is given at a dose of 20 mg sc qd, which is identical to the dose found to be effective in relapsing-remitting MS. Patients will be seen at three month intervals for clinical evaluation, and will have yearly MRI scans.